The overall objective of the work described in this proposal is to determine the molecular basis of antigenic variation in influenza B viruses compared with antigenic drift in influenza A. A detailed understanding of the mechanism(s) of antigenic variation will enable development of effective vaccines to control the disease. The specific aims are: 1. To determine if the sequences of the hemagglutinin genes of influenza B viruses isolated from human epidemics correlate with their antigenic properties. 2. To determine if the antigenic structure of the influenza B hemagglutinin is different to that of influenza A. 3. To determine if the multiple changes we have found in influenza B hemagglutinin variants are significant in the epidemiology of influenza B. 4. To determine if the differences in antigenicity of the hemagglutinin between influenza A and B also found in the other surface antigen of the virus, the neuraminidase.